Prostate cancer radiation response signature predicts radiation benefit in breast cancer: post hoc analysis of SweBCG91RT

PORTOS is a 24-gene radiation response signature developed and validated in randomized trials in prostate cancer. Given its basis in general radiation and DNA damage response pathways, PORTOS might be able to predict benefit from radiation therapy (RT) in breast cancer. In a post hoc analysis, PORTOS scores were calculated from gene expression profiles of 765 tumor samples from SweBCG91RT, a randomized trial of adjuvant whole-breast RT versus observation following breast-conserving surgery in node-negative stage I-IIA breast cancer. The primary endpoint was 10-year cumulative incidence (CI) of any recurrence. A significant interaction (p=0.049) between PORTOS and RT was observed for 10-year CI of any recurrence. Patients in the top 75% of PORTOS scores derived substantial benefit from RT (sHR 0.46; p<0.001) compared to those in the bottom 25% (sHR 0.73; p=0.24). Higher PORTOS scores were also associated with increased risk of RT-related breast pain, though the interaction p-value was not significant (p=0.07). PORTOS was weakly anti-correlated with tumor size, histologic grade, and tumor-infiltrating leukocytes. The authors conclude that PORTOS predicts benefit from RT for any recurrence in early-stage breast cancer, mirroring it performance in prostate cancer.